Circulating Microparticles are increased amongst people presenting with HIV and advanced immune suppression in Malawi and correlate closely with arterial stiffness

Objectives We aim to investigate whether circulating microparticle (CMPs) subsets were raised amongst people presenting with HIV and advanced immune suppression in Malawi, and whether they associated with arterial stiffness. Methods ART-naïve adults with a new HIV diagnosis and CD4 <100 cells/µL had microparticle characterisation and carotid femoral Pulse Wave Velocity (cfPWV) at 2 weeks post ART initiation. HIV uninfected controls were matched on age, systolic BP and diastolic BP in a 1:1 ratio. Circulating microparticles were identified from platelet poor plasma and stained for endothelial, leucocyte, monocyte and platelet markers. Results The median (IQ) total CMP count was 1 log higher in participants with HIV compared to those without (p<0.0001) and was associated with arterial stiffness (spearman rho 0.47, p<0.001). In adjusted analysis, every log increase in circulating particles showed a 20% increase in cfPWV (95% CI 4 – 40%, p=0.02). In terms of subsets, endothelial and platelet derived microparticles were most strongly associated with HIV. Endothelial derived E-selectin+ CMPs were 1.3log-fold higher and platelet derived CD42a+ CMPs were 1.4log-fold higher (both p<0.0001). Endothelial and platelet derived CMPs also correlated most closely with arterial stiffness [spearman rho: E-selectin+ 0.57 and CD42a 0.56, both p<0.0001). Conclusions Circulating microparticles associate strongly with arterial stiffness among PLWH in Malawi. Endothelial damage and platelet activation are of particular importance and future translational studies should consider prioritising this pathway. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This work was supported by a Wellcome Trust Clinical PhD Training Fellowship \[grant number 099934/Z/12/A], a strategic award from the Wellcome Trust for the MLW Clinical Research Programme and core support to the MRC Clinical Trials Unit at UCL [MC\_UU\_12023/23\] \[MC\_UU\_12023/26\]. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: All participants provided informed written consent and ethical approval was granted by the College of Medicine Research and Ethics Committee (COMREC), University of Malawi (P.09/13/1464) and the University of Liverpool Research and Ethics Committee (UoL000996). All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes All relevant data is included in the published manuscript or supporting material